Abstract
FF domains are evolutionarily conserved but present in a limited number of proteins, predominantly in RNA regulatory proteins, including transcription and splicing factors, and in some members of the p190 family of guanosine triphosphatase (GTPase) activating proteins (GAPs) for Rho. Jiang et al. report that the FF domain of p190A RhoGAP (p190A) mediates the sequestration of the serum-responsive transcription factor TFII-1 in the cytosol under nonstimulated conditions. TFII-1 was found as a binding partner for the FF domains of p190A RhoGAP in a glutathione- S -transferase (GST) fusion protein pull-down assay, and the interaction was verified using purified proteins in vitro and by coimmunoprecipitation from serum-starved mouse fibroblasts. In a reporter gene assay, cotransfection of p190A with GST-TFII-1 inhibited expression of the TFII-1-regulated reporter gene compared with that observed for cells transfected only with GST-TFII-1. Based on immunofluorescence assays and cell fractionation assays, in cells deficient for p190A, TFII-1 was localized in the nucleus under serum-starved conditions and after the addition of platelet-derived growth factor (PDGF), whereas in wild-type cells TFII-1 was distributed in both the cytosol and the nucleus and PDGF triggered the redistribution of TFII-1 to a predominantly nuclear localization. A PDGF consensus phosphorylation sequence is present in the first FF domain of 190A, and treatment of cells with serum or PDGF stimulates the phosphorylation of p190A. FF domain phosphorylation mutants were used to demonstrate that phosphorylation of 190A controls the ability of 190A to sequester TFII-1. Thus, these results suggest a GAP-independent function in the regulation of transcription for members of the 190 RhoGAP family that have FF domains. W. Jiang, R. Sordella, G.-C. Chen, S. Hakre, A. L. Roy, J. Settleman, An FF domain-dependent protein interaction mediates a signaling pathway for growth factor-induced gene expression. Mol. Cell 17 , 23-35 (2005). [PubMed]
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